Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety and immunogenicity of an Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid vaccine (PRP-D) has been evaluated when administered alone or simultaneously with other vaccines in over 1,400 2-24 month old subjects. In the first infant study, groups of subjects received either the PRP-D, PRP or placebo vaccine at 3, 5 and 7 months, one month after DPT immunization at 2, 4 and 6 months of age. In a subsequent study infants received either the PRP-D or PRP vaccine simultaneously with DPT. Safety of the PRP-D vaccine was indistinguishable from that of the PRP and placebo vaccines. In both studies, greater than 90% of the PRP-D recipients developed protective levels of antibody (greater than 0.15 microgram/ml) and the majority developed greater than 1.0 microgram/ml of anti-PRP. Following a booster dose of PRP-D at 14-18 months, simultaneously with either MMR, DPT or polio vaccine, all children in these studies developed greater than 1.0 micrograms/ml of antibody. Several other administration schedules have been evaluated in separate clinical studies. Acceptability of a combined DPT/PRP-D vaccine is currently being evaluated in experimental studies.
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PMID:Studies on the combined administration of Haemophilus influenzae type B--diphtheria toxoid conjugate vaccine (PRP-D) and DTP. 354 93

To evaluate the safety and immunogenicity of the Haemophilus influenzae type b polysaccharide vaccine, PRP, and a new polysaccharide-diphtheria toxoid conjugate vaccine, PRP-D, a collaborative study was carried out in six centers in five states. Subjects were 585 infants 15 to 24 months of age. They were randomly assigned to receive a single dose of PRP or PRP-D vaccine. There were no significant differences in the rate of adverse reactions between the two vaccine groups. Minor local reactions occurred in 10.3% of PRP and 12.5% of PRP-D recipients, and fever in 27.4% of PRP and 23.8% of PRP-D recipients. All reactions resolved within 48 hours. Serum samples were obtained just before vaccination and after 1 month. Prevaccination antibody levels were similar for the PRP (0.035 micrograms/mL) and PRP-D (0.027 micrograms/mL) groups, with no differences in levels by age, sex, race, vaccine lot, or study site. Both groups had significant rises in geometric mean levels, but this difference was significantly greater for PRP-D (2.166 micrograms/mL) than for PRP (0.154 micrograms/mL). In addition, the percentage of responders as determined by three definitions (twofold titer rise, greater than 0.15 micrograms/mL, and greater than 1.0 micrograms/mL) was also significantly greater for PRP-D than PRP. In contrast to a marked age-related immunogenicity to PRP (P less than 0.001), there was no significant variation in immune response to PRP-D by age. PRP-D conjugate vaccine appears to be as safe and significantly more immunogenic than PRP vaccine for children vaccinated at 15 to 24 months of age.
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PMID:Safety and immunogenicity of Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children 15 to 24 months of age. 355 21

Sixty 9- to 15-month-old infants were randomly assigned to receive two doses, 1 month apart, of a Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) or PRP vaccine, each containing 20 micrograms PRP. There were no significant local or systemic reactions. After one dose of PRP-D, 93% of the subjects attained levels of greater than or equal to 0.15 microgram/ml and 59% achieved greater than or equal to 1 microgram/ml antibody protein. These percentages rose to 100% and 86%, respectively, after the second dose, at which time the geometric mean titer of anti-PRP antibody was 4.8 micrograms/ml. IgG anti-PRP levels were 4.3 times higher than IgM. The proportion of IgG to IgM antibody induced by PRP-D increased with age. After two doses, 33% of the PRP recipients responded with a level of greater than or equal to 0.15 microgram/ml and only 19% responded to a level of greater than or equal to 1.0 microgram/ml. One year later, all of the PRP-D recipients tested still had greater than or equal to 0.15 microgram/ml and more than half had greater than or equal to 1.0 microgram/ml antibody protein.
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PMID:Safety and immunogenicity of Haemophilus influenzae type b-polysaccharide diphtheria toxoid conjugate vaccine in infants 9 to 15 months of age. 387 77

We measured the uptake of radiolabeled Haemophilus influenzae type b by human polymorphonuclear leukocytes. Haemophilus influenzae type b strains were preopsonized in individual sera from six adults immunized with type b polysaccharide vaccine (PRP) or six adults immunized with PRP covalently coupled to diphtheria toxoid (PRP-D vaccine). Serum was heat inactivated before use, and exogenous human complement was added. Of the 12 subjects, 3 had high levels of opsonic activity (greater than 40% of immune control) in their preimmunization serum. This activity did not correlate with the concentrations of anti-PRP antibody and was unaffected by absorption of anti-PRP antibody. At 1 month after vaccination, the serum of PRP-D subjects had higher opsonic activity than that from subjects who received PRP (5% serum, mean PRP-D = 86%, mean PRP = 53%, P = 0.001). After 12 months, both groups had higher serum opsonic activity than before immunization (P less than 0.02), but there was no difference between the two groups (mean PRP-D = 48%, mean PRP = 51%). In postimmunization serum, opsonic activity induced by PRP-D or PRP vaccines correlated directly with anti-PRP antibody concentrations as measured by a radioantigen binding assay. We conclude that both vaccines induce opsonic activity, opsonic activity induced by immunization of adults correlates well with the concentration of anti-PRP antibody achieved, and in preimmune sera with low concentrations of anti-PRP antibody, factors other than anti-PRP antibody contribute to opsonic activity.
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PMID:Serum opsonic activity after immunization of adults with Haemophilus influenzae type b-diphtheria toxoid conjugate vaccine. 387 63

Haemophilus influenzae type b (Hib) capsular polysaccharide (PRP) was selectively hydrolyzed to reducing oligosaccharides, and the fraction containing 3-10 ribosylribitolphosphate repeating units (VS) was conjugated by reductive amination to diphtheria toxin (DTx), its nontoxic derivative CRM197 (Dcr), or diphtheria toxoid (DTd). Conjugate DTx-VS retained approximately 1% of native toxicity, which was eliminated by treatment with formalin. Immunization of rabbits with the conjugates elicited antibody (Ab) to PRP and to DTx but not to a model for the linkage determinant. Human adults given single subcutaneous injections had rises in serum Ab to PRP and in bactericidal activity in vitro; the Ab protected infant rats challenged with Hib. Adults had rises also in Ab to DTd, and these Ab protected rabbits against DTx. A series of two injections of the conjugates Dcr-VS and DTd-VS was tested in infants beginning at 19-23 mo of age. Rises in anti-PRP Ab after the primary resembled the rises after PRP vaccine. In contrast to PRP, the conjugates elicited large rises after the secondary vaccinations and a substantial IgG component. Development of bactericidal activity paralleled the rises in anti-PRP Ab. Secondary rises after Dcr-VS were higher than after DTd-VS. In infants 12-16 mo of age, Dcr-VS (but not DTd-VS) elicited strong primary and secondary Ab responses that included IgG and bactericidal activity. Both conjugates produced consistent rises in Ab to DTd.
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PMID:Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197. 387 82

We studied an immunogen consisting of oligosaccharides derived from Haemophilus influenzae type b capsular polysaccharide (PRP) coupled to CRM197, a nontoxic relative of diphtheria toxin. Subcutaneous injections were given to eight subjects at ages 2, 4, and 6 months, simultaneously with conventional diphtheria-tetanus-pertussis (DTP) vaccine. After the first immunization, total serum anti-PRP antibodies declined in all subjects, but increased in most after the second immunization and after the third in seven of seven subjects analyzed. In these seven infants, the geometric mean level at age 9 months (0.73 micrograms/ml) exceeded by at least 40 times the means of historical control groups given DTP only or DTP plus (uncoupled) PRP vaccine. An isotype-specific assay showed that IgM antibodies increased after the first immunization with the coupled vaccine in all eight infants. Against the background of declining maternal IgG antibody, elevations in IgG antibody were detected after the second or third immunization in six of the eight. These six at age 9 to 11 months were immunized with (uncoupled) PRP vaccine, and a "boost" in anti-PRP antibody, including an IgG component, was found.
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PMID:Immunization of 2-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b. 387 5

Samples of CSF, serum, and urine from 162 children with a clinical diagnosis of possible bacterial infection were examined by CIE within 1 hr of admission to the hospital. Results obtained were compared to information derived from gram stain and bacterial cultures of these specimens. Thirty-eight of 59 patients with culturally proved bacterial infections had positive CIE determinations at the time of admission. Highest correlation between culture and CIE results was in patients with meningitis due to Hemophilus influenzae type b while poorest correlation was obtained in children with pneumococcal septicemia. PRP within serum or CSF was quantitated on 21 occasions in patients with H. influenzae meningitis. Patients who experienced sequelae of their meningitis had significantly (p less than 0.005-0.025) higher levels of PRP within CSF and serum than those whose recovery was uneventful.
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PMID:Countercurrent immunoelectrophoresis in the evaluation of childhood infections. 415 36

Seventy-eight Navajo infants (one to two months of age) were randomly assigned to one of two vaccination groups: one group (40 infants) was scheduled to receive three doses of diphtheria-pertussis-tetanus (DPT) vaccine and the other (38 infants) to receive DPT combined with Haemophilus influenzae type b polyribosyl-ribitol phosphate (DPT + PRP vaccine). In the latter vaccine, pertussis antigen served as an adjuvant for PRP. Sixty-seven infants (37 who received DPT vaccine and 30 who received DPT + PRP vaccine) completed the protocol. Local and systemic reactions were equally frequent in the two groups. Fifty percent of the infants who received DPT + PRP vaccine had definite antibody responses to PRP after three doses, and 13% had possible responses. Of the infants who received DPT vaccine, 14% and 8% had definite and possible responses, respectively; three of five infants with definite responses were infected with H influenzae type b or cross-reacting organisms, as determined by pharyngeal cultures. The immune response did not appear to be suppressed by the presence of maternal antibody.
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PMID:Immunogenicity of a Haemophilus influenzae type b vaccine in combination with diphtheria-pertussis-tetanus vaccine in infants. 631 13

Siblings of patients with type b Haemophilus influenzae meningitis are at increased risk of developing Haemophilus disease. We immunized 26 healthy siblings and 25 control subjects using a vaccine containing the type b polysaccharide capsule (10 micrograms PRP) and pertussis vaccine (4 opacity units) (Lederle Laboratories) to determine whether siblings of patients with Haemophilus meningitis had an impaired antibody response to PRP. Using two intramuscular injections one month apart, we found that the siblings had a lower response to PRP. One month after the second injection, 12 of 24 of the siblings had serum concentrations of anticapsular (PRP) antibody thought to be sufficient to confer protection against Haemophilus disease (greater than or equal to 300 ng/ml), compared with 19 of 24 of the control children tested (50% vs 79%, P = 0.035 by chi-square analysis). In comparison with the normal controls, the siblings produced significantly less IgG anti-PRP antibody but similar amounts of IgM. The impaired responsiveness to PRP was most evident among the 16 children born after their sibling had meningitis and who were not known to have been exposed to type b Haemophilus infection previously. These data indicate that siblings of some patients with type b Haemophilus meningitis have reduced ability to form IgG anti-PRP antibody, which may be associated with increased susceptibility to Haemophilus disease.
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PMID:Siblings of patients with Haemophilus meningitis have impaired anticapsular antibody responses to Haemophilus vaccine. 660 4

The capsular polysaccharide of Haemophilus influenzae type b is a poor immunogen in human infants. In an attempt to enhance immunogenicity, this polysaccharide was covalently coupled to diphtheria toxoid and the conjugate tested as a vaccine in adult volunteers. Two injections of PRP-D vaccine were given, separated by one month. The anti-PRP antibody responses in this group were compared with those in a group receiving a comparable dose (20 micrograms) of conventional PRP vaccine. Both vaccines were well tolerated. A single injection of PRP-D was significantly more immunogenic than PRP, eliciting higher serum concentrations of total anti-PRP antibody 1 month later (geo means of 248 and 62 micrograms/ml, respectively; P less than 0.001). In addition, higher concentrations of IgG anti-PRP antibody were observed in the PRP-D group (P less than 0.001). One month after reinjection of vaccine, subjects receiving PRP-D showed a small but significant decline in total antibody (P = 0.03), whereas the serum antibody concentrations in the group that received PRP remained unchanged. At 12 months, the antibody concentrations of the two groups were not significantly different. Bactericidal activity and passive protection activity (infant rat model) were tested in pooled sera from the three highest and three lowest responders in each vaccine group; both PRP and PRP-D vaccines induced biologically active anti-PRP antibody. Thus PRP-D was found to elicit biologically active serum antibody and to be more immunogenic in adults than PRP vaccine; however, the duration of higher concentrations of antibody was transient.
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PMID:Immunogenicity of Haemophilus influenzae type b polysaccharide--diphtheria toxoid conjugate vaccine in adults. 661 Jul 36


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